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Category: genetics

Study examines oligodendrocyte dynamics throughout the progression of multiple sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by the disruption of nerve signals and various associated neurological symptoms, ranging from vision problems to numbness, weakness, fatigue and cognitive impairments. These symptoms emerge when the immune system starts to attack mature oligodendrocytes (MOLs), specialized cells that produce the protective sheath surrounding nerve fibers (i.e., myelin).

There are several subtypes of MOLs, which might exhibit different immune cell-like genetic responses in patients diagnosed with MS. While various studies have investigated the neural and molecular underpinnings of MS, how these different cell subtypes respond as the disease progresses has not yet been elucidated.

Researchers at Karolinska Institute in Sweden recently carried out a mouse study aimed at mapping how different MOL subtypes might differ in their sensitivity to neuroinflammation across different stages of MS.

Hidden cellular layers in the brain’s memory center

Using a powerful RNA labeling method called RNAscope with high-resolution microscopy imaging, the team captured clear snapshots of single-molecule gene expression to identify CA1 cell types inside mouse brain tissue. Within 58.065 CA1 pyramidal cells, they visualized more than 330,000 RNA molecules—the genetic messages that show when and where genes are turned on. By tracing these activity patterns, the researchers created a detailed map showing the borders between different types of nerve cells across the CA1 region of the hippocampus.

The results showed that the CA1 region consists of four continuous layers of nerve cells, each marked by a distinct set of active genes. In 3D, these layers form sheets that vary slightly in thickness and structure along the length of the hippocampus. This clear, layered pattern helps make sense of earlier studies that saw the region as a more gradual mix or mosaic of cell types.

“When we visualized gene RNA patterns at single-cell resolution, we could see clear stripes, like geological layers in rock, each representing a distinct neuron type,” said a co–first author of the paper. “It’s like lifting a veil on the brain’s internal architecture. These hidden layers may explain differences in how hippocampal circuits support learning and memory.”

The hippocampus is among the first regions affected in Alzheimer’s disease and is also implicated in epilepsy, depression, and other neurological conditions. By revealing the CA1’s layered structure, the study provides a roadmap to investigate which specific neuron types are most vulnerable in these disorders.

The new CA1 cell-type atlas, built using data from the Hippocampus Gene Expression Atlas (HGEA), is freely available to the global research community. The dataset includes interactive 3D visualizations accessible through the Schol-AR augmented-reality app, which allows scientists to explore hippocampal layers in unprecedented detail.

Researchers have identified a previously unknown pattern of organization in one of the brain’s most important areas for learning and memory. The study, published in Nature Communications, reveals that the CA1 region of a mouse’s hippocampus, a structure vital for memory formation, spatial navigation, and emotions, has four distinct layers of specialized cell types. This discovery changes our understanding of how information is processed in the brain and could explain why certain cells are more vulnerable in diseases like Alzheimer’s and epilepsy.

Continue reading “Hidden cellular layers in the brain’s memory center” | >

Protein unties tangled DNA linked to hotspots of cancer mutations

New research published in Nature Communications has linked a normal cellular process to an accumulation of DNA mutations in cancer and identified cancer-driving mutations in an underexplored part of the genome.

Led by Dr. Jüri Reimand of the Ontario Institute for Cancer Research (OICR), the study centers around a protein called TOP2B, part of a family of enzymes that serve an important function in cells and are targets of common cancer chemotherapies.

Strands of DNA are long and complex, and they often get looped and tangled. When that happens, TOP2B and other topoisomerase proteins make cuts to DNA strands to help untangle and repair them. But Reimand and colleagues found many genetic mutations present at the sites of these cuts.

A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one’s susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS. Several mechanisms have been suggested to explain the potential role of the microbiome in the etiology of AS, such as alterations of intestinal permeability, stimulation of immune responses, and molecular mimicry.

Scientists identify first non-coding gene that controls cell size

What keeps our cells the right size? Scientists have long puzzled over this fundamental question, since cells that are too large or too small are linked to many diseases. Until now, the genetic basis behind cell size has largely been a mystery. New research has, for the first time, identified a gene in the non-coding genome that can directly control cell size.

In a study published in Nature Communications, a team at The Hospital for Sick Children (SickKids) found that a gene called CISTR-ACT acts as a controller of cell growth. Unlike genes that encode for proteins, CISTR-ACT is a long non-coding RNA (or lncRNA) and is part of the non-coding genome, the largely unexplored part that makes up 98% of our DNA. This research helps show that the non-coding genome, often dismissed as “junk DNA,” plays an important role in how cells function.

“Our study shows that long non-coding RNAs and the non-coding regions of the genome can drive important biological processes, including cell size regulation. By carefully examining a wide range of cell types and phenotypes, we identified the first causal long non-coding RNA that directly influences cell size,” says Dr. Philipp Maass, Senior Scientist in the Genetics & Genome Biology program at SickKids, and Canada Research Chair in Non-Coding Disease Mechanisms.

Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch

Mammals display prominent diversity in the ability to regenerate damaged ear pinna, but the genetic changes underlying the failure of regeneration remain elusive. We performed comparative single-cell and spatial transcriptomic analyses of rabbits and mice recovering from pinna damage. Insufficient retinoic acid (RA) production, caused by the deficiency of rate-limiting enzyme Aldh1a2 and boosted RA degradation, was responsible for the failure of mouse pinna regeneration. Switching on Aldh1a2 or RA supplementation reactivated regeneration. Evolutionary inactivation of multiple Aldh1a2-linked regulatory elements accounted for the deficient Aldh1a2 expression upon injury in mice and rats. Furthermore, the activation of Aldh1a2 by a single rabbit enhancer was sufficient to improve ear pinna regeneration in transgenic mice.

Elevated mtDNA copy number in older adults is linked to methylation of mitochondrial and nuclear regulatory regions

Growing evidence shows that epigenetic modification and mitochondrial dysfunction are hallmarks of aging and are associated with the development of a wide range of age-related diseases. Mitochondrial biogenesis, which is marked by mitochondrial DNA copy number (mtDNAcn), is one of the major regulations of mitochondrial function by a set of transacting elements, including mitochondrial DNA polymerase gamma (POLG), working on the mtDNA control region. In this study, we investigated the mtDNAcn and the methylation status at both mtDNA control and POLGA promoter regions in human blood cells from individuals with a wide range of ages. A total of 119 blood samples were collected, including 24 umbilical cord blood samples from newborns and 95 peripheral blood samples from individuals aged 18 to 96 years.

Molecular Switch for Repairing Central Nervous System disorders

A molecular switch has the ability to turn on a substance in animals that repairs neurological damage in disorders such as multiple sclerosis (MS), Mayo Clinic researchers discovered. The early research in animal models could advance an already approved Food and Drug Administration therapy and also could lead to new strategies for treating diseases of the central nervous system.

Research by Isobel Scarisbrick, Ph.D., published in the Journal of Neuroscience finds that by genetically switching off a receptor activated by blood proteins, named Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin, a fatty substance that coats and protects nerves.

“Myelin regeneration holds tremendous potential to improve function. We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system does have a good capacity for innate repair,” says Dr. Scarisbrick, principal investigator and senior author. “This sets the stage for development of new clinically relevant myelin regeneration strategies.”

Psychiatric Disorders Share Far More DNA Than Scientists Realized

A global research team co-led by VCU expert Kenneth Kendler has produced the most comprehensive genetic map so far, identifying five families of disorders that show a high degree of overlap. An international team of scientists is offering new insight into why people are so often affected by more

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